Kinetic characterization of 13NH3 and [13N]glutamine metabolism in rabbit heart.

The isolated arterially perfused rabbit interventricular septum was used to study the effects of methionine sulfoximine (MSO) on 13N-labeled ammonia (13NH3) and 13N-labeled glutamine [( 13N]gln) metabolism. Tissue time-activity curves were generated from bolus injections of 13NH3 or [13N]gln delivered interarterially during control conditions and in the presence of MSO. The fraction of 13N label retained in the tissue [EF(3)] was significantly (P less than 0.01) less after a bolus of [13N]gln than 13NH3. MSO significantly (P less than 0.05) decreased the EF(3) after a bolus of 13NH3 or [13N]gln. Chemical analyses using high-pressure liquid chromatography on tissue and effluent samples obtained after bolus injections of 13NH3 and [13N]gln with or without MSO present showed the following: 1) after a bolus of 13NH3 or [13N]gln the tissue 13N label is predominantly in [13N]gln at 6 min after injection, and 2) MSO significantly decreases the synthesis of [13N]gln after an 13NH3 bolus. Thus it would appear that the glutamine synthetase reaction is primarily responsible for the retention of the 13N label from 13NH3 as [13N]gln in rabbit myocardium.